Epidemiological studies have associated low birth weight (LBW) and more specifically, intrauterine growth retardation with the subsequent development of insulin resistance. Type 2 diabetes mellitus, hypertension, coronary artery disease, and lower cognitive performance later in life. It is postulated that nutritional experiences during critical periods of development may "program" long-term structure or function of an organism and, hence, permanently alter physiology later in life. Nutritional programming has been demonstrated convincingly in a variety of animal models. Brief periods of early dietary manipulation, particularly variations in carbohydrate (CHO) intake, have lifelong effects on health. However, in humans, programming has been difficult to prove, largely because active interventions are difficult; most studies have been retrospective, epidemiological surveys. Ideally, a convincing case for programming can be made, if it can be demonstrated that as a consequence of early differences in nutrition, the response of an individual to a physiologic or biochemical stimulus is demonstrably altered later in life. We have access to a unique population of 63 LBW infants who were prospectively fed one of five rigidly controlled diets that differed in the absolute amounts and relative proportions of fat and CHO intake. Protein intake was constant over the course of the 4-8 weeks of experimental feeding. These subjects, who demonstrated striking diet-related differences in numerous physiological, biochemical and behavioral variables as neonates, are now 7-8 years old and potentially available for follow up studies, including stimulus response experiments. Our working hypothesis is that increased exposure to CHO intake during early life is associated with insulin resistance, increased fat mass and circulating serum lipids, improved cognitive performance at 7-8 years and reduced fat oxidation. Demonstration that significant changes in these variables are linked to early CHO intake would provide important evidence linking early nutritional practices and vulnerability to adult onset diseases.